Advantages of nanocarriers for basic research in the field of traumatic brain injury

A major challenge for the efficient treatment of traumatic brain injury is the need for therapeutic molecules to cross the blood-brain barrier to enter and accumulate in brain tissue.To overcome this problem,researchers have begun to focus on nanocarriers and other brain-targeting drug delivery systems.In this review,we summarize the epidemiology,basic pathophysiology,current clinical treatment,the establishment of models,and the evaluation indicators that are commonly used for traumatic brain injury.We also report the current status of traumatic brain injury when treated with nanocarriers such as liposomes and vesicles.Nanocarriers can overcome a variety of key biological barriers,improve drug bioavailability,increase intracellular penetration and retention time,achieve drug enrichment,control drug release,and achieve brain-targeting drug delivery.However,the application of nanocarriers remains in the basic research stage and has yet to be fully translated to the clinic.

Targeting brain tumors with innovative nanocarriers:bridging the gap through the blood-brain barrier

Background:Glioblastoma multiforme(GBM)is recognized as the most lethal and most highly invasive tumor.The high likelihood of treatment failure arises fromthe presence of the blood-brain barrier(BBB)and stemcells around GBM,which avert the entry of chemotherapeutic drugs into the tumormass.Objective:Recently,several researchers have designed novel nanocarrier systems like liposomes,dendrimers,metallic nanoparticles,nanodiamonds,and nanorobot approaches,allowing drugs to infiltrate the BBB more efficiently,opening up innovative avenues to prevail over therapy problems and radiation therapy.Methods:Relevant literature for this manuscript has been collected from a comprehensive and systematic search of databases,for example,PubMed,Science Direct,Google Scholar,and others,using specific keyword combinations,including“glioblastoma,”“brain tumor,”“nanocarriers,”and several others.Conclusion:This review also provides deep insights into recent advancements in nanocarrier-based formulations and technologies for GBM management.Elucidation of various scientific advances in conjunction with encouraging findings concerning the future perspectives and challenges of nanocarriers for effective brain tumor management has also been discussed.

Stimuli-Responsive Gene Delivery Nanocarriers for Cancer Therapy

Gene therapy provides a promising approach in treating cancers with high efficacy and selectivity and few adverse effects.Currently,the development of functional vectors with safety and effectiveness is the intense focus for improving the delivery of nucleic acid drugs for gene therapy.For this purpose,stimuli-responsive nanocarriers displayed strong potential in improving the overall efficiencies of gene therapy and reducing adverse effects via effective protection,prolonged blood circulation,specific tumor accumulation,and controlled release profile of nucleic acid drugs.Besides,synergistic therapy could be achieved when combined with other therapeutic regimens.This review summarizes recent advances in various stimuliresponsive nanocarriers for gene delivery.Particularly,the nanocarriers responding to endogenous stimuli including pH,reactive oxygen species,glutathione,and enzyme,etc.,and exogenous stimuli including light,thermo,ultrasound,magnetic field,etc.,are introduced.Finally,the future challenges and prospects of stimuli-responsive gene delivery nanocarriers toward potential clinical translation are well discussed.The major objective of this review is to present the biomedical potential of stimuli-responsive gene delivery nanocarriers for cancer therapy and provide guidance for developing novel nanoplatforms that are clinically applicable.

Colon cancer and their targeting approaches through nanocarriers:A review

Colon cancer is the fifth most common type of cancer in the world.Colon cancer develops when healthy cells in the lining of the colon or rectum alter and grow uncontrollably to form a mass known as a tumor.Despite major medical improvements,colon cancer is still one of the leading causes of cancer-related mortality globally.One of the main issues of chemotherapy is toxicity related to conventional medicines.The targeted delivery systems are considered the safest and most effective by increasing the concentration of a therapeutic substance at the tumor site while decreasing it at other organs.Therefore,these delivery systems required lower doses for high therapeutic value with minimum side effects.The current review focuses on targeting therapeutic substances at the desired site using nanocarriers.Additionally,the diagnostic applications of nanocarriers in colorectal cancer are also discussed.

Nanocarriers as a powerful vehicle to overcome blood-brain barrier in treating neurodegenerative diseases: Focus on recent advances

Neurodegenerative diseases including Alzheimer’s disease,Parkinson’s disease,Huntington disease and amyotrophic lateral sclerosis throw a heavy burden on families and society. Related scientific researches make tardy progress. One reason is that the known pathogeny is just the tip of the iceberg. Another reason is that various physiological barriers,especially blood-brain barrier(BBB),hamper effective therapeutic substances from reaching site of action. Drugs in clinical treatment of neurodegenerative diseases are basically administered orally. And generally speaking,the brain targeting efficiency is pretty low. Nanodelivery technology brings hope for neurodegenerative diseases. The use of nanocarriers encapsulating molecules such as peptides and genomic medicine may enhance drug transport through the BBB in neurodegenerative disease and target relevant regions in the brain for regenerative processes. In this review,we discuss BBB composition and applications of nanocarriers-liposomes,nanoparticles,nanomicelles and new emerging exosomes in neurodegenerative diseases. Furthermore,the disadvantages and the potential neurotoxicity of nanocarriers according pharmacokinetics theory are also discussed.

Phage display: development of nanocarriers for targeted drug delivery to the brain

The blood brain barrier represents a formidable obstacle for the transport of most systemati- cally administered neurodiagnostics and neurotherapeutics to the brain. Phage display is a high throughput screening strategy that can be used for the construction of nanomaterial peptide libraries. These libraries can be screened for finding brain targeting peptide ligands. Surface functionalization of a variety of nanocarriers with these brain homing peptides is a sophisticated way to develop nanobiotechnology-based drug delivery platforms that are able to cross the blood brain barrier. These efficient drug delivery systems raise our hopes for the diagnosis and treatment of various brain disorders in the future.

Flavonoids Loaded in Nanocarriers: An Opportunity to Increase Oral Bioavailability and Bioefficacy

Flavonoids are among the biggest group of polyphenols, widely distributed in plant-based foods. A plethora of evidence supports the health benefits and value of flavonoids can play in the physiological function treatment and in the prevention of disease particularly in the prevention of degenerative conditions including cancers, cardiovascular and neurodegenerative diseases. Hence, flavonoids represent the active constituents of many dietary supplements and herbal remedies, as well as there is an increasing interest in this class of polyphenols as functional ingredients of beverages, food grains and dairy products. Conversely, various studies have also shown that flavonoids have some drawbacks after oral administration such as stability, bioavailability and bioefficacy. This article reviews the current status of novel nanodelivery systems including nanospheres, nanocaspsules, micro- and nanoemulsions, micelles, solid lipid nanoparticles and nanostructured lipid capsules, successfully developed for overcoming the delivery challenges of flavonoids.

Gene transfection mediated by polyethyleneiminepolyethylene glycol nanocarrier prevents cisplatininduced spiral ganglion cell damage

Polyethyleneimine-polyethylene glycol （PEI-PEG）, a novel nanocarrier, has been used for trans- fection and gene therapy in a variety of cells. In our previous study, we successfully carried out PEI-PEG-mediated gene transfer in spiral ganglion cells. It remains unclear whether PEI-PEG could be used for gene therapy with X-linked inhibitor of apoptosis protein （XIAP） in the inner ear. In the present study, we performed PEI-PEG-mediated XIAP gene transfection in the cochlea of Sprague-Dawley rats, via scala tympani fenestration, before daily cisplatin injections. Audito- ry brainstem reflex tests demonstrated the protective effects of XIAP gene therapy on auditory function. Immunohistochemical staining revealed XIAP protein expression in the cytoplasm of cells in the spiral ganglion, the organ of Corti and the stria vascularis. Reverse transcription-PCR detected high levels of XIAP mRNA expression in the cochlea. The present findings suggest that PEI-PEG nanocarrier-mediated XIAP gene transfection results in XIAP expression in the cochlea, prevents damage to cochlear spiral ganglion cells, and protects hearing.

Synergism of essential oils with lipid based nanocarriers: emerging trends in preservation of grains and related food products

Grains are one of the major food staples in the world.The cereal grains are easily susceptible to damage by moisture content,flour beetles and food pathogens during storage,harvesting and post harvesting.Food preservative techniques namely drying,freezing,and dehydration,acquire little advantages.However,they cause few undesirable alterations in the organoleptic and nutritional properties of the preserved food items.Therefore,there is a continuous search for new preservation techniques in food industries,to satisfy the customer demands on the addition of natural food preservatives,devoid of pathogenic contaminants and without changes in organoleptic properties.Essential oils(EOs)have been predicted as“natural food additives”in the preservative process.The synergistic potential of EOs with various nanocarriers plays an emerging role in the food industry.Therefore,the present review has focused on the lipid based nanocarriers,and the methods used for the functionalization or encapsulation of EOs and applications in the preservation of food items such as cooked rice,rice flour,grains,sliced breads have also been discussed.The present review ascertains the antimicrobial significance of active EOs loaded lipid nanocarriers in the form of nano emulsions,solid lipid nanoparticles and liposomes for preserving grains and flours.

An understanding of mitochondria and its role in targeting nanocarriers for diagnosis and treatment of cancer

Nanotechnology has changed the entire paradigm of drug targeting and has shown tremendous potential in the area of cancer therapy due to its specificity. In cancer, several targets have been explored which could be utilized for the better treatment of disease. Mitochondria, the so-called powerhouse of cell, portrays significant role in the survival and death of cells, and has emerged as potential target for cancer therapy. Direct targeting and nanotechnology based approaches can be tailor-made to target mitochondria and thus improve the survival rate of patients suffering from cancer. With this backdrop, in present review, we have reemphasized the role of mitochondria in cancer progression and inhibition, highlighting the different targets that can be explored for targeting of disease. Moreover, we have also summarized different nanoparticulate systems that have been used for treatment of cancer via mitochondrial targeting.

Microwave technology enabled transdermal nanocarrier and drug delivery

Transdermal drug delivery is impeded by the natural barrier of epidermis known as stratum corneum.This limits the route to transport of drugs with a log octanol–water partition coefficient of 1 to 3,molecular weight of less than 500 Da and melting point of less than 200°C.Nanotechnology has received a widespread investigation as the nanocarriers are able to fluidize the stratum corneum as a function of size,shape,surface charges,and hydrophilicity–hydrophobicity balance,while delivering drugs across the skin barrier.

Stimuli-responsive nanocarriers for therapeutic applications in cancer

Cancer has become a very serious challenge with aging of the human population.Advances in nanotechnology have provided new perspectives in the treatment of cancer.Through the combination of nanotechnology and therapeutics,nanomedicine has been successfully used to treat cancer in recent years.In terms of nanomedicine,nanocarriers play a key role in delivering therapeutic agents,reducing severe side effects,simplifying the administration scheme,and improving therapeutic efficacies.Modulations of the structure and function of nanocarriers for improved therapeutic efficacy in cancer have attracted increasing attention in recent years.Stimuli-responsive nanocarriers penetrate deeply into tissues and respond to external or internal stimuli by releasing the therapeutic agent for cancer therapy.Notably,stimuli-responsive nanocarriers reduce the severe side effects of therapeutic agents,when compared with systemic chemotherapy,and achieve controlled drug release at tumor sites.Therefore,the development of stimuli-responsive nanocarriers plays a crucial role in drug delivery for cancer therapy.This article focuses on the development of nanomaterials with stimuli-responsive properties for use as nanocarriers,in the last few decades.These nanocarriers are more effective at delivering the therapeutic agent under the control of external or internal stimuli.Furthermore,nanocarriers with theranostic features have been designed and fabricated to confirm their great potential in achieving effective treatment of cancer,which will provide us with better choices for cancer therapy.

Impact of chitosan-based nanocarriers on cytoskeleton dynamics:Current status and challenges

Chitosan-based nanocarriers(CS-NCs)show a promising role in improving drugs and bioactive compounds delivery for therapy.However,the effects exerted by CS-NCs at the cellular level,including their recognition and uptake,have not been fully investigated yet.Many factors,including size,shape,concentration,and surface chemistry of CS-NCs,play an important role in determining the types of intracellular signals triggered.The mechanism of uptake and the involvement of the cytoskeleton during the CS-NCs endocytosis variates among the different cell types as well as further effects observed inside cells.In the present work,we discuss the effects induced by CS-NCs per se on the cytoskeleton,a key component in cell architecture and physiology.The focus of this report is made on tumoral and normal biological models in which CS-NCs could differentially affect the cell cytoskeleton.The recent years reports regarding the impact of CS-NCs on cytoskeleton dynamics and the current techniques for its evaluation are summarized and discussed.Understanding mechanisms underlying cytoskeletal impact after cell exposure to CS-NCs is critical for the design of safest value-added formulations in the biomedical field.Furthermore,this revision points out some interesting aspects of cytoskeletal changes and cell death encompassing anti-tumoral effects.

Delivery of siRNA/miRNA by nanocarriers to treat colon cancer

Despite the current advances in the discovery of the colorectal cancer biomarkers and in the diagnosis and treatment of CRC, the incidence and mortality of colon cancer are still increasing year by year. At present, many patients with colon cancer have been diagnosed in an advanced stage, which always accompanied by liver metastasis and distant metastasis. However, current treatments for advanced colon cancer are limited. Therefore, the delivery of siRNA/miRNA to colon cancer lesions may be a new approach to the treatment of colon cancer. This review provides ideas for the molecular treatment of colon cancer by discussing the biological characteristics of colon cancer and the regulation of important miRNA molecules in colon cancer. Moreover, this review describes the development of nanocarriers in recent years and the important role of nanocarrier materials in the targeted delivery of small molecules. On the one hand, nanocarriers can serve as small carriers or siRNA/miRNAs, and on the other hand, can transport small molecules or siRNA/miRNAs into colon cancer cells, thereby regulating key genes expression affecting colon cancer cell proliferation, metastasis, and apoptosis. Delivery of siRNA/miRNA via nanocarriers may be a novel approach to the treatment of colon cancer.

Anti-cancer drugs targeting using nanocarrier niosomes-a review

In the last few decades numbers of review and research articles have been published on niosomes. This shows the relevant interest of academias & researchers in niosomes because of the advantages sponsored by them over other colloidal drug delivery systems. Niosomes formation occurs when non-ionic surfactant vesicles assemble themselves. Various antineoplastic agents are used in chemotherapy, but they have some drawbacks that these agents cause cell death in normal tissues as well. There are two approaches to overcome this limitation. First, to modify the structure of existing drugs, but this will not possible because it changes the properties of drugs. Second, the development of nano-carriers like liposomes, dendrimers, nanoparticles, niosomes et al. Among all, niosomes (non-ionic surfactant vesicles) have more advantages besides all nano-carriers. Drugs either hydrophilic in nature or hydrophobic in nature, both can be incorporated in niosomes. And by embedding specific ligands over vesicular surface enables us to target the drug to specific cancer cells.

Microenvironment responsive pod-structured astaxanthin nanocarrier for ameliorating inflammatory bowel disease

Anti-inflammatory drugs targeting inflammatory bowel disease(IBD)have attracted considerable attention but still face low therapeutic outcomes and frequent side effects.Astaxanthin(ATX),a natural ketone,possesses potent antioxidant and anti-inflammatory properties.However,it faces problems such as poor water solubility,photothermal instability,and low bioavailability.Here,we employed a supramolecular encapsulation strategy to create a nanoscale oral delivery system for ATX(referred to as FC-ATX NPs)by coupling fucoidan(FUC)with chitosan oligosaccharides(COS).The obtained FC-ATX NPs exhibited a particular“bean pod”structure with uniform size,good encapsulation efficiency,excellent physical and chemical stability,pH-triggered intestinal targeted slow-release properties,and potent antioxidant capacity.In vitro cell culture experiments showed that FC-ATX NPs promoted cellular uptake and scavenged excessive intracellular reactive oxygen species(ROS).In mouse models of colitis,FC-ATX NPs enhanced the drug absorption of intestinal epithelial cells and effectively accumulated at the site of inflammation.This work provides an efficient approach to enhance the bioavailability of ATX and has excellent application potential as an oral targeted delivery system for colitis therapy.

Julolidinyl aza-BODIPYs as NIR-Ⅱ fluorophores for the bioimaging of nanocarriers

The aggregation-caused quenching(ACQ)rationale has been employed to improve the fluorescence imaging accuracy of nanocarriers by precluding free probe-derived interferences.However,its usefulness is undermined by limited penetration and low spatiotemporal resolution of NIR-Ⅰ(700-900 nm)bioimaging owing to absorption and diffraction by biological tissues and tissue-derived autofluorescence.This study aimed to develop ACQ-based NIR-Ⅱ(1000-1700 nm)probes to further improve the imaging resolution and accuracy.The strategy employed is to install highly planar and electron-rich julolidine into the 3,5-position of aza-BODIPY based on the larger substituent effects.The newly developed probes displayed remarkable photophysical properties,with intense absorption centered at approximately 850 nm and bright emission in the 950-1300 nm region.Compared with the NIR-Ⅰ counterpart P2,the NIR-Ⅱ probes demonstrated superior water sensitivity and quenching stability.ACQ1 and ACQ6 exhibited more promising ACQ effects with absolute fluorescence quenching at water fractions above 40% and higher quenching stability with less than 2.0% fluorescence reillumination in plasma after 24 h of incubation.Theoretical calculations verified that molecular planarity is more important than hydrophobicity for ACQ properties.Additionally,in vivo and ex vivo reillumination studies revealed less than 2.5% signal interference from prequenched ACQ1,in contrast to 15% for P2.

Exosome-biomimetic nanocarriers for oral drug delivery

Exosomes as authigenous nanovesicles secreted by living cells represent a significant class of biomaterials.By virtue of their unique roles in intercellular communication,exosomes can mediate intercellular information/cargoes exchange as messenger and facilitate drug delivery as smart vehicles.Oral medication is the most clinically relied upon route of administration and can achieve both topical and systemic therapeutic effects after absorption.Exosomes and exosome-derived vectors have shown to be of high value in oral drug delivery,since they enable efficient oral delivery of therapeutic molecules by targeting intestinal epithelial cells.In recent years,exosome-biomimetic nanocarriers have emerged as an important catalyzer in innovating oral drug delivery systems.In this work,we roundly reviewed the biogenesis and functions of exosomes,their extraction and characterization methods,resources available for exosomes harvest,and design philosophy of exosome-derived vehicles,particularly highlighting the oral delivery application of exosome-biomimetic nanocarriers for diverse medicines.Accumulating evidence suggests that exosome-biomimetic nanocarriers hold great promise for oral delivery of intractable drugs with potential biopharmaceutic issues.

Viral and nonviral nanocarriers for in vivo CRISPR-based gene editing

The continued development of clustered regularly interspaced short palindromic repeats(CRISPR)technology has the potential to greatly impact clinical medicine,particularly for disease diagnosis and treatment.Despite high demand for the in vivo delivery of CRISPR-based therapies,significant challenges persist.These include rapid degradation by enzymes,inefficient disease site targeting,and the risk of undesired off-target outcomes.Nanoparticulate platforms,with their tailorable properties,have been engineered to efficiently package CRISPR payloads in various formats,including as plasmid DNA,mRNA,and ribonucleoprotein complexes,for in vivo delivery.Among them,recombinant adeno-associated viruses,virus-like particles,and lipid nanoparticles have displayed exceptional promise.This review will discuss the development of these and other nanocarriers for in vivo CRISPR-based genome editing.